Molecular Aspects of Medicine,
Journal Year:
2023,
Volume and Issue:
95, P. 101231 - 101231
Published: Dec. 5, 2023
Liver
fibrosis,
as
an
excess
deposition
of
extracellular
matrix
(ECM)
components,
results
from
chronic
liver
injury
well
persistent
activation
inflammatory
response
and
fibrogenesis.
fibrosis
is
a
major
determinant
for
disease
(CLD)
progression
in
the
last
two
decades
our
understanding
on
molecular
cellular
mechanisms
underlying
fibrogenic
CLD
has
dramatically
improved,
boosting
pre-clinical
studies
clinical
trials
designed
to
find
novel
therapeutic
approaches.
From
these
several
critical
concepts
have
emerged,
starting
reveal
complexity
pro-fibrotic
microenvironment
which
involves
very
complex,
dynamic
interrelated
interactions
between
different
hepatic
extrahepatic
cell
populations.
This
review
will
offer
first
recapitulation
established
pathophysiological
basic
principles
by
intentionally
focus
attention
NAFLD/NASH,
metabolic-related
form
with
high
impact
general
population
emerging
leading
cause
worldwide.
NAFLD/NASH-related
pro-inflammatory
profibrogenic
be
analysed
information
cells,
mediators
signalling
pathways
taken
advantage
methodological
approaches
techniques
(single
genomics,
imaging
mass
cytometry,
vitro
two-
three-dimensional
models,
etc.).
We
next
overview
recent
advancement
diagnostic
prognostic
tools,
including
serum
biomarkers
polygenic
scores,
support
analysis
biopsies.
Finally,
this
provide
current
therapies
treatment
NAFLD/NASH
patients.
Obesity Facts,
Journal Year:
2024,
Volume and Issue:
17(4), P. 374 - 444
Published: Jan. 1, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD),
previously
termed
non-alcoholic
fatty
(NAFLD),
is
defined
as
(SLD)
in
the
presence
of
one
or
more
cardiometabolic
risk
factor(s)
and
absence
harmful
alcohol
intake.
The
spectrum
MASLD
includes
steatosis,
metabolic
steatohepatitis
(MASH,
NASH),
fibrosis,
cirrhosis
MASH-related
hepatocellular
carcinoma
(HCC).
This
joint
EASL-EASD-EASO
guideline
provides
an
update
on
definitions,
prevention,
screening,
diagnosis
treatment
for
MASLD.
Case-finding
strategies
with
using
non-invasive
tests,
should
be
applied
individuals
factors,
abnormal
enzymes,
and/or
radiological
signs
hepatic
particularly
type
2
diabetes
(T2D)
obesity
additional
factor(s).
A
stepwise
approach
blood-based
scores
(such
FIB-4)
and,
sequentially,
imaging
techniques
transient
elastography)
suitable
to
rule-out/in
advanced
which
predictive
liver-related
outcomes.
In
adults
MASLD,
lifestyle
modification
-
including
weight
loss,
dietary
changes,
physical
exercise
discouraging
consumption
well
optimal
management
comorbidities
use
incretin-based
therapies
(e.g.
semaglutide,
tirzepatide)
T2D
obesity,
if
indicated
advised.
Bariatric
surgery
also
option
obesity.
If
locally
approved
dependent
label,
non-cirrhotic
MASH
significant
fibrosis
(stage
≥2)
considered
a
MASH-targeted
resmetirom,
demonstrated
histological
effectiveness
acceptable
safety
tolerability
profile.
No
pharmacotherapy
can
currently
recommended
cirrhotic
stage.
Management
adaptations
drugs,
nutritional
counselling,
surveillance
portal
hypertension
HCC,
transplantation
decompensated
cirrhosis.
Journal of Hepatology,
Journal Year:
2023,
Volume and Issue:
79(5), P. 1317 - 1331
Published: Aug. 9, 2023
The
farnesoid
X
receptor
(FXR),
a
bile
acid
(BA)-activated
nuclear
highly
expressed
in
the
liver
and
intestine,
regulates
expression
of
genes
involved
cholesterol
homeostasis,
hepatic
gluconeogenesis,
lipogenesis,
inflammation
fibrosis,
addition
to
controlling
intestinal
barrier
integrity,
preventing
bacterial
translocation
maintaining
gut
microbiota
eubiosis.
Non-alcoholic
steatohepatitis
(NASH),
an
advanced
stage
non-alcoholic
fatty
disease,
is
characterized
by
steatosis,
hepatocyte
damage
(ballooning)
inflammation,
leading
cirrhosis
hepatocellular
carcinoma.
NASH
represents
major
unmet
medical
need,
but
no
pharmacological
treatments
have
yet
been
approved.
pleiotropic
mechanisms
development
offer
range
therapeutic
opportunities
among
them
FXR
activation
has
emerged
as
established
target.
Various
agonists
with
different
physicochemical
properties,
which
can
be
broadly
classified
BA
derivatives,
non-BA-derived
steroidal
agonists,
non-steroidal
partial
are
clinical
development.
In
this
review
we
will
summarize
key
preclinical
features
most
critically
evaluate
their
potential
treatment.
World Journal of Hepatology,
Journal Year:
2023,
Volume and Issue:
15(2), P. 180 - 200
Published: Feb. 24, 2023
Chronic
liver
disease
(CLD)
is
a
continuous
process
that
causes
reduction
of
function
lasting
more
than
six
months.
CLD
includes
alcoholic
(ALD),
non-alcoholic
fatty
(NAFLD),
chronic
viral
infection,
and
autoimmune
hepatitis,
which
can
lead
to
fibrosis,
cirrhosis,
cancer.
Liver
inflammation
oxidative
stress
are
commonly
associated
with
the
development
progression
CLD.
Molecular
signaling
pathways
such
as
AMP-activated
protein
kinase
(AMPK),
C-Jun
N-terminal
kinase,
peroxisome
proliferator-activated
receptors
(PPARs)
implicated
in
pathogenesis
Therefore,
antioxidant
anti-inflammatory
agents
from
natural
products
new
potent
therapies
for
ALD,
NAFLD,
hepatocellular
carcinoma
(HCC).
In
this
review,
we
summarize
some
powerful
be
potential
applied
all
stages
CLD,
ALD/NAFLD
HCC.
The
selected
β-sitosterol,
curcumin,
genistein,
silymarin
regulate
activation
several
important
molecules,
including
AMPK,
Farnesoid
X
receptor,
nuclear
factor
erythroid
2-related
factor-2,
PPARs,
phosphatidylinositol-3-kinase,
lysyl
oxidase-like
proteins.
addition,
clinical
trials
undergoing
evaluate
their
efficacy
safety.
Metabolism,
Journal Year:
2024,
Volume and Issue:
157, P. 155937 - 155937
Published: May 21, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
closely
associates
with
obesity
and
type
2
diabetes.
Lifestyle
intervention
bariatric
surgery
aiming
at
substantial
weight
loss
are
cornerstones
of
MASLD
treatment
by
improving
histological
outcomes
reducing
risks
comorbidities.
Originally
developed
as
antihyperglycemic
drugs,
incretin
(co-)agonists
SGLT2
inhibitors
also
reduce
steatosis
cardiorenovascular
events.
Certain
agonists
effectively
improve
features
MASLD,
but
not
fibrosis.
Of
note,
beneficial
effects
on
may
necessarily
require
loss.
Despite
moderate
gain,
one
PPARγ
agonist
improved
adipose
tissue
certain
benefit
fibrosis
in
post-hoc
analyses.
Likewise,
the
first
THRβ-agonist
was
recently
provisionally
approved
because
significant
improvements
We
here
discuss
liver-related
metabolic
induced
different
treatments
their
association
Therefore,
we
compare
results
from
clinical
trials
drugs
acting
via
(incretin
(co)agonists,
inhibitors)
those
exerting
no
(pioglitazone;
resmetirom).
Furthermore,
other
development
directly
targeting
hepatic
lipid
metabolism
(lipogenesis
inhibitors,
FGF21
analogs)
addressed.
Although
THRβ-agonism
outcomes,
concepts
should
consider
all
cardiometabolic
risk
factors
for
effective
reduction
morbidity
mortality
affected
people.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Jan. 24, 2024
Abstract
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
a
substantial
contributor
to
liver-related
morbidity
worldwide,
and
yet,
there
are
no
standard,
universal
pharmacologic
therapies
approved
for
this
indication.
The
aim
of
systematic
review
meta-analysis
evaluate
the
effectiveness
SGLT-2
inhibitors
in
improving
hepatic
steatosis
fibrosis
patients
with
NAFLD.
An
extensive
electronic
database
search
was
done
identify
studies
published
from
inception
until
December
2023,
without
any
language
restrictions.
All
randomized
controlled
trials
(RCT)
that
evaluated
use
NAFLD,
regardless
diabetes
mellitus
status,
were
included.
Cochrane
Risk
Bias
2.0
tool
used
assess
risk
bias
each
study
Evidence
all
synthesized
as
mean
differences
continuous
data,
ratio
dichotomous
outcomes.
inverse
variance
or
Mantel–Haenszel
test
conjunction
random-effects
model,
where
necessary.
18
eligible
RCTs
involving
1330
participants
analyzed,
which
had
ranging
low
some
concerns.
Significant
difference
means
observed
attenuation
parameter
(6
trials,
n
=
372;
MD:
−
10.59
dB/m,
95%
CI
[−
18.25,
2.92],
p
0.007,
I
2
0%);
L/S
(3
163;
0.11,
[0.01,
0.21],
0.04,
78%);
LSM
(7
447;
0.67
kPa,
1.19,
0.16],
0.010,
69%);
MRI-PDFF
(5
330;
2.61%,
5.05,
0.17],
78%),
FIB-4
index
(10
648;
0.12,
0.21,
0.04],
0.005,
16%)
after
inhibitor
treatment
compared
controls.
In
conclusion,
may
lead
slight
improvement
and/or
controls
NAFLD
Type
based
on
imaging
histopathology
biomarkers
moderate
certainty
evidence.
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(1), P. 140 - 140
Published: Jan. 17, 2025
Non-alcoholic
fatty
liver
disease
(NAFLD)
has
become
the
most
common
chronic
and
is
closely
associated
with
metabolic
diseases
such
as
obesity,
type
2
diabetes
mellitus
(T2DM),
syndrome.
However,
effective
treatment
strategies
for
NAFLD
are
still
lacking.
In
recent
years,
progress
been
made
in
understanding
pathogenesis
of
NAFLD,
identifying
multiple
therapeutic
targets
providing
new
directions
drug
development.
This
review
summarizes
advances
focusing
on
mechanisms
action
natural
products,
small-synthetic-molecule
drugs,
combination
therapy
strategies.
aims
to
provide
insights
treating
NAFLD.
